Honing in on her target

Dr Nikki Verrills' research into a key
signalling switch in cancer cells could provide an important breakthrough in
treatment.

As a young
undergraduate studying science, Dr Nikki Verrills had intentions of
transferring to medicine. Then, she discovered a passion for laboratory
research and realised she could effectively fight disease on another front.

"In the end
I have achieved the best of both worlds," the biochemist and cancer researcher points
out. "I am still in the medical field helping patients by contributing to the
development of better treatments but I am also able to pursue my interest in
lab work, which I find fascinating."

Verrills has
certainly found her niche. Since completing her PhD in 2005 she has worked
largely full-time in academic research, collecting a clutch of early career
awards, fellowships and major grants in recognition of her groundbreaking
research into leukaemia and breast cancer. She studies the molecular pathways
of cancer, identifying genes and proteins in cancer cells in order to make
comparisons between normal cells and
cancer cells. She also analyses differences between cancer cells that respond
well to drug treatments and those that do not.

"If scientists
can identify proteins that are different in cancerous cells, or in
drug-resistant cells, then we can design drugs to target those differences –
drugs that will specifically kill cancerous cells but not normal cells," she explains.
"That is fundamental cancer research, but most cancer drugs work by turning off
a particular protein, or inactivating it. What is novel about our work is that
we have targeted a protein that needs to be switched back on."

That protein
is phosphatase 2A, or PP2A, which comes from a class of proteins known as
'tumour suppressors'. Normally, they act as a stop signal to inhibit the growth
of cancerous cells. In leukaemia cells, however, PP2A is inactive, so the
cancer cells continue to proliferate.

In 2007,
Verrills worked with collaborators in the United States to prove that the drug
FTY720 could effectively switch PP2A on in patients with chronic myeloid
leukaemia (CML) – therefore stopping the cancer's spread without affecting the
body's healthy cells. This year she was awarded a $360,000 grant from the Cure
Cancer Australia Foundation and Cancer Council NSW to apply that research to a
different cancer, acute myeloid leukaemia (AML), which has a very poor survival
rate.

"There is a
real urgency to find new treatments for AML because the vast majority of
patients are resistant to chemotherapy and will die of the disease," Verrills asserts.
The grant will allow Verrills and her team to test FTY720 and other drugs in
different sub-types of AML, and move their work from the laboratory into
clinical trials.

"Another
focus of our work is establishing exactly how these types of drugs work," she outlines.
"We know the end result is that they increase activity of PP2A but we want to
advance the knowledge in this field by finding out specifically how they do
that. Also, we know from literature that this class of proteins is important in
a lot of solid tumours, so it is likely that this research will be applicable
to other cancers as well."

Verrills has
received ongoing support from high-profile national cancer organisations and
has forged collaborations with key research groups in Australia and
internationally. She also works closely with colleagues in the University's Centres
for Cancer and Chemical Biology and through her links with the Hunter Medical
Research Institute (HMRI) has established important working relationships with
cancer specialists and haematologists. Her articles are published in internationally
prominent journals and she has been recognised with a Voiceless Eureka Prize
for Research for her commitment to minimising the use of animals in laboratory
work.

Verrills'
doctoral studies into chemotherapy resistance in childhood leukaemia led to a
Peter Doherty Postdoctoral Fellowship from the National Health and Medical
Research Council in 2006. In the same year she was the inaugural recipient of a
Hunter Medical Research Foundation grant for young cancer researchers. She is
currently supported by an Early Career Researcher Fellowship with the Cancer
Institute of NSW.

Verrills
gained exposure during her doctoral studies to cutting-edge scientific
techniques used at the Australian Proteomic Analysis Facility, in Sydney,
becoming one of the first researchers in the country to use Difference In-Gel
Electrophoresis (DIGE). This technique allows simultaneous analysis of proteins
in cancerous, non-cancerous and control cells and vastly improves the
efficiency and accuracy of testing.

The
scientist admits that work/life balance is an elusive concept given her
demanding research career, two young daughters and family interest in a
vineyard (in which her husband Michael De Iuliis, a fellow scientist, is chief
winemaker). But she praises the support of the University of Newcastle, which
has allowed her to maintain the momentum of her research while juggling life's
other commitments.

"Not only
has the University supported me but it has also shown a lot of confidence in
me, which is critical for career advancement," Verrills acknowledges. "I have
my own research group and I have reached the stage of being an independent
researcher much earlier than I probably would have anywhere else."

Career Summary

Biography

Dr Verrills research interests centre on understanding the signalling pathways involved in cancer development, progression and resistance to chemotherapy induced cell death. Her research involves cell biology and biochemistry, translation into clinically relevant mouse models of disease, and analysis of primary patient samples. During her PhD studies Dr Verrills used powerful proteomics techniques, including being one of the first in Australia to use difference in-gel electrophoresis (DIGE) technology, to discover novel protein alterations that confer chemotherapy resistance in childhood leukaemia.

In postdoctoral studies Dr Verrills further applied her proteomics skills to the investigation of respiratory disease, and has identified clinical biomarkers for asthma and chronic obstructive pulmonary disease. These proteins are now targets for patent applications and ongoing investigations into the development of diagnostics and improved therapies. Her postdoctoral studies in respiratory disease led to an interest in signalling pathways, with particular interest in the multifunctional protein phosphatase, PP2A. This led her to establish a research group investigating the role of protein phosphatase 2A (PP2A) in cellular functions. Her group has discovered novel roles for PP2A in cellular function and disease, including myeloid leukaemias, melanoma and asthma, and demonstrated that PP2A activation is a potential strategy for improved therapies (e.g. senior author papers in Cancer Research and Cell Signalling, and co-authored papers in Nature Medicine, Journal of Clinical Investigation; J Biol Chem; BBA; Cell Death & Diff). She has developed a unique panel of PP2A molecular reagents (shRNA, overexpression constructs, antibodies, pharmacological activators/inhibitors), and established strategic collaborations which has enabled her to expand her investigations of PP2A into the study of breast cancer.

Her PhD was awarded from Macquarie University in 2005, for which she received a Vice-Chancellor’s Commendation for Excellencein Research. In 2006 Dr Verrills received a highly competitive NHMRC Peter Doherty Postdoctoral Fellowship. Through this fellowship she also received a scholarship to the Australian Academy of Science “Science at the Shine Dome” meeting. In 2006 she also became the inaugural recipient of the Hunter Medical Research Institute (HMRI) Competitive Research Fund for Early Career Researchers in Cancer. In 2010 Dr Verrills was appointed to an ongoing academic position (Lecturer) at the University of Newcastle, however in 2011 she was awarded a Cancer Institute NSW Early Career Research Development Award, and after deferring this for a year for maternity leave, she took up this fellowship in Dec 2011.

Research outputs: Dr Verrills has 28 research publications, with 13 as first or senior author, appearing in journals of good to high impact in the field (average IF 6.4) and are well cited (>800 to date; average 59 cites/yr; h-index 14). The importance of her work has also been featured in editorial articles (Fojo, T (2006) J Natl Cancer Inst 98: 1363 and Ojima and Ferlini (2003) Chem Biol 10: 583).

Funding: Since 2006 Dr Verrills has attracted >$3M in competitive research grant/fellowship funding, from the NHMRC, Cancer Council NSW, Anthony Rothe Foundation, Ramaciotti Foundation, Cancer Institute NSW, Cure Cancer Australia Foundation, and the Hunter Medical Research Institute (HMRI). She has also attracted infrastructure funding from the ARC, ACRF, Ramaciotti Foundation and the Cancer Institute NSW of > $6.4M.

Awards: Dr Verrills research is internationally competitive and recognised through continued publications, presentations at international and national meetings, and international and national awards. These include the 2012 Newcastle Innovations ‘Rising Star Award’; 2010 HUPO Young Guns Award; 2007 Voiceless Eureka Prize; the 2007 Young Tall Poppy Award; the 2007 University of Newcastle Vice Chancellor’s Award for Research Excellence; 2004 Biochemical Journal Young Investigator Award, presented to the best young researcher at the 12th International Conference on Second Messengers and Phosphoproteins, Montreal, Canada; the Merck Sharp Dohm “Best of the Best” Award and the Cure Cancer Australia Foundation Award, both presented at the 2004 Australian Health and Medical Research (ASMR) Congress. In 2003 Dr Verrills was awarded the University of Sydney Medal forExcellence in Medical Research, presented to the best young researcher at the ASMR NSW Conference, and was a finalist in the Cure Cancer Australia Foundation’s Young Researcher of the Year Award.

Service to the discipline: Her expertise in the field of proteomics and cancer biology results in invitations to peer review grant applications (e.g. NHMRC, ARC, Wellcome Trust; AICR; Cure Cancer Australia Foundation), ~20 manuscripts/year for a variety of journals (e.g. Blood, Oncogene, Cancer Research; Molecular Cancer Therapeutics; Proteomics), and ~2 PhD theses/year. In 2012 and 2013 Dr Verrills was a panel member for the NHMRC Cancer Biology & Oncology grant review panel. She has also served on the Leukaemia Foundation PhD and Postdoctoral fellowship review panels. Dr Verrills is a mentor in a University run mentoring program for early career researchers, and has given many lectures to undergraduate, graduate, and school students on careers in medical research.

Invited presentations: In 2012 Dr Verrills was an invited speaker at the International meetings: Phophatases in Disease, Vic; 37th Annual Lorne Proteins Meeting, Vic; Garvan Signalling Meeting, Sydney; Australian Society for Medical Research (ASMR) NSW Branch Scientific Meeting, Sydney. She was also session chair for the ASMR NSW Branch Scientific Meeting and the New Directions in Leukaemia Research, Sunshine Coast. She regularly presents her research to other universities and research institutes. For example, in 2012 she presented at the Lowy Cancer Centre, UNSW, in 2010 at IMVS, Adelaide, and at Pharmaxis in Sydney. In past years she has presented at Macquarie University, The Oncology Research Unit, Westmead, and the Children’s Cancer Institute Australia, Sydney.

Student Supervision: Dr Verrills has been primary supervisor for 3 PhD students to completion, and a further student recently submitted. These students received a number of awards during their studies. She has supervised four Honours students (all received 1st Class).

Conference coordination: Dr Verrills was co-convenor for the international meeting: HMRI Translational Cancer Conference – Pathways to Tailored Therapies, Newcastle, 2008, and was on the organising committee for the 2006 HMRI Conference on Translational Cancer Research and again for the 2013 Conference.

Committees: Dr Verrills is an active member of the Hunter Medical Research Institute Cancer Research Program Steering committee, where she has taken a major role in building up the activities of the program including preparing strategic plans, infrastructure and program funding applications, inviting speakers and establishing an annual research seminar day to foster internal research collaborations. She is also a member of the University of Newcastle’s Australian Biomolecular Research Facility steering committee.

Community engagement: She has a strong commitment to the advancement and promotion of medical research in our society. As part of her community involvement she has disseminated her research through the print, radio, and television media, and has presented her research to the local community as a guest speaker at Rotary and Lions Clubs, and HMRI, Cure Cancer Australia, and Cancer Council NSW charity events. Through the Tall Poppy Campaign she has also presented her research to High School students across NSW, and has established relationships with her local school communities to foster and encourage an interest in studying science.

Current position: In Dec 2011 Dr Verrills returned from maternity leave as a Research Only Academic at the University of Newcastle, working 0.6FTE, funded by a Cancer Institute NSW ECR Development Award.

Research ExpertiseDr Verrills research interests centre on understanding the molecular changes involved in cancer progression and chemotherapy resistance. By using powerful proteomics techniques, including being one of the first in Australia to use difference in-gel electrophoresis (DIGE) technology, she has discovered novel protein alterations that confer chemotherapy resistance in childhood leukaemia. These proteins are now targets for ongoing investigations to develop improved therapies for relapsed leukaemia patients. Dr Verrills is currently investigating the role of the signaling protein, protein phosphatase 2A, in cancer. Using shRNA and overexpression transfection of normal and cancer cell lines, coupled with molecular and biochemical analyses such as PCR, immunoblotting, immunoprecipitation, immunofluorescence, 2D-DIGE and mass spectrometry, she is determining the role of mutant PP2A and specific PP2A subunits in the development of leukaemia and breast cancer.

Teaching ExpertiseDr Verrills is a strong supporter of fostering research students. She has supervised two Honours student (both received 1st Class), and is currently supervising one Honours and three PhD students. Dr Verrills is a fulltime research academic, however she does guest lecture for 2nd and 3rd year BBiomed Sci courses in Proteomics, Bioinformatics, Cancer, and Drug Resistance.

Administrative ExpertiseDr Verrills undetakes many administrative tasks, including managing the budgets for her grants. Some duties include obtaining product quotes, ordering, safety and ethics applications, co-ordinating multi investigator grant applications, and organising research seminar series and workshops.

Qualifications

Bachelor of Science (Honours), Macquarie University

Keywords

Breast Cancer

Cancer

Chemotherapy resistance

Drug resistance

Leukaemia

Protein phosphatase 2A

Proteomics

Signal transduction

Fields of Research

Code

Description

Percentage

060199

Biochemistry and Cell Biology not elsewhere classified

75

111599

Pharmacology and Pharmaceutical Sciences not elsewhere classified

15

111299

Oncology and Carcinogenesis not elsewhere classified

10

Professional Experience

UON Appointment

Title

Organisation / Department

Senior Lecturer

University of NewcastleSchool of Biomedical Sciences and PharmacyAustralia

Academic appointment

Dates

Title

Organisation / Department

21/05/2015 - 21/06/2015

Postdoctoral Scientist

University of NewcastleAustralia

1/01/2012 - 31/12/2013

Membership - NHMRC Grant Review Panel

NHMRC Grant Review PanelAustralia

1/01/2011 -

Fellow

University of NewcastleSchool of Biomedical Sciences and PharmacyAustralia

Amersham Biosciences Technical Seminar Series. Brisbane; Adelaide; Melbourne; Sydney. Organisation: GE Biosciences
Description:
Amersham Biosciences, now part of GE Healthcare, is a world leader in proteomics technology. I was invited as an expert presenter on the use of state of the art proteomic technology, 2D difference gel electrophoresis, and how this technology can be applied in biomedical research.

2002

New technologies meets functional proteomics. Organisation: ComBio 2002
Description:
This was a special session at the ComBio meeting convened bythe Australian Proteomics Society and was an invited speaker.

Two University of Newcastle (UON) cancer researchers from the School of Biomedical Sciences and Pharmacy in the Faculty of Health and Medicine have been awarded more than $1 million in Cancer Council NSW project grants for 2015.

Dr Nikki Verrills

Position

Senior LecturerSchool of Biomedical Sciences and PharmacyFaculty of Health and Medicine